Morphometric measurements can improve prediction of progressive vertebral deformity following vertebral damage.

PURPOSE: A damaged vertebral body can exhibit accelerated 'creep' under constant load, leading to progressive vertebral deformity. However, the risk of this happening is not easy to predict in clinical practice. The present cadaveric study aimed to identify morphometric measurements in a damaged vertebral body that can predict a susceptibility to accelerated creep. METHODS: A total of 27 vertebral trabeculae samples cored from five cadaveric spines (3 male, 2 female, aged 36 to 73 (mean 57) years) were mechanically tested to establish the relationship between bone damage and residual strain. Compression testing of 28 human spinal motion segments (three vertebrae and intervening soft tissues) dissected from 14 cadaveric spines (10 male, 4 female, aged 67 to 92 (mean 80) years) showed how the rate of creep of a damaged vertebral body increases with increasing "damage intensity" in its trabecular bone. Damage intensity was calculated from vertebral body residual strain following initial compressive overload using the relationship established in the compression test of trabecular bone samples. RESULTS: Calculations from trabecular bone samples showed a strong nonlinear relationship between residual strain and trabecular bone damage intensity (R2 = 0.78, P < 0.001). In damaged vertebral bodies, damage intensity was then related to vertebral creep rate (R2 = 0.39, P = 0.001). This procedure enabled accelerated vertebral body creep to be predicted from morphological changes (residual strains) in the damaged vertebra. CONCLUSION: These findings suggest that morphometric measurements obtained from fractured vertebrae can be used to quantify vertebral damage and hence to predict progressive vertebral deformity.

Importance of the epiphyseal ring in OLIF stand-alone surgery: a biomechanical study on cadaveric spines.

PURPOSES: To explore the function of endplate epiphyseal ring in OLIF stand-alone surgery using a biomechanical model to reduce the complications of endplate collapse and cage subsidence. METHODS: In total, 24 human cadaveric lumbar function units (L1-2 and L3-4 segments) were randomly assigned to two groups. The first group was implanted with long fusion cages which engaged with both inner and outer regions of epiphyseal ring (Complete Span-Epiphyseal Ring, CSER). Those engaged with only the inner half of epiphyseal ring were the second group (Half Span-Epiphyseal Ring, HSER). Each group was divided into two subgroups [higher cage-height (HH) and normal cage-height (NH)]. Specimens were fixed in testing cups and compressed at approximately 2.5 mm/s, until the first sign of structural failure. Trabecular structural damage was analyzed by Micro-CT, as well as the difference of bone volume fraction (BV/TV), trabecular thickness (Tb.Th) et al. in different regions. RESULTS: Endplate collapse was mainly evident in the inner region of epiphyseal ring, where trabecular injury of sub-endplate bone was most concentrated. Endplate collapse incidence was significantly higher in HSER than CSER specimens (P = 0.017). A structural failure occurred at a lower force in HSER (1.41 ± 0.34 KN) compared with CSER (2.44 ± 0.59 KN). HH subgroups failed at a lower average force than NH subgroups. Micro-CT results showed a more extensive trabecular fracture in HSER specimens compared to CSER specimens, especially in HH subgroup. CONCLUSIONS: Endplate collapse is more likely to occur with short half span cages than complete span cages, and taller cages compared with normal height cages. During OLIF surgery, we should choose cages matching intervertebral disc space height and place the cages spanning over the whole epiphyseal ring to improve support strength.

Nerves and blood vessels in degenerated intervertebral discs are confined to physically disrupted tissue.

Nerves and blood vessels are found in the peripheral annulus and endplates of healthy adult intervertebral discs. Degenerative changes can allow these vessels to grow inwards and become associated with discogenic pain, but it is not yet clear how far, and why, they grow in. Previously we have shown that physical disruption of the disc matrix, which is a defining feature of disc degeneration, creates free surfaces which lose proteoglycans and water, and so become physically and chemically conducive to cell migration. We now hypothesise that blood vessels and nerves in degenerated discs are confined to such disrupted tissue. Whole lumbar discs were obtained from 40 patients (aged 37-75 years) undergoing surgery for disc herniation, disc degeneration with spondylolisthesis or adolescent scoliosis ('non-degenerated' controls). Thin (5-µm) sections were stained with H&E and toluidine blue for semi-quantitative assessment of blood vessels, fissures and proteoglycan loss. Ten thick (30-µm) frozen sections from each disc were immunostained for CD31 (an endothelial cell marker), PGP 9.5 and Substance P (general and nociceptive nerve markers, respectively) and examined by confocal microscopy. Volocity image analysis software was used to calculate the cross-sectional area of each labelled structure, and its distance from the nearest free surface (disc periphery or internal fissure). Results showed that nerves and blood vessels were confined to proteoglycan-depleted regions of disrupted annulus. The maximum distance of any blood vessel or nerve from the nearest free surface was 888 and 247 µm, respectively. Blood vessels were greater in number, grew deeper, and occupied more area than nerves. The density of labelled blood vessels and nerves increased significantly with Pfirrmann grade of disc degeneration and with local proteoglycan loss. Analysing multiple thick sections with fluorescent markers on a confocal microscope allows reliable detection of thin filamentous structures, even within a dense matrix. We conclude that, in degenerated and herniated discs, blood vessels and nerves are confined to proteoglycan-depleted regions of disrupted tissue, especially within annulus fissures.

Why do some intervertebral discs degenerate, when others (in the same spine) do not?

This review suggests why some discs degenerate rather than age normally. Intervertebral discs are avascular pads of fibrocartilage that allow movement between vertebral bodies. Human discs have a low cell density and a limited ability to adapt to mechanical demands. With increasing age, the matrix becomes yellowed, fibrous, and brittle, but if disc structure remains intact, there is little impairment in function, and minimal ingrowth of blood vessels or nerves. Approximately half of old lumbar discs degenerate in the sense of becoming physically disrupted. The posterior annulus and lower lumbar discs are most affected, presumably because they are most heavily loaded. Age and genetic inheritance can weaken discs to such an extent that they are physically disrupted during everyday activities. Damage to the endplate or annulus typically decompresses the nucleus, concentrates stress within the annulus, and allows ingrowth of nerves and blood vessels. Matrix disruption progresses by mechanical and biological means. The site of initial damage leads to two disc degeneration "phenotypes": endplate-driven degeneration is common in the upper lumbar and thoracic spine, and annulus-driven degeneration is common at L4-S1. Discogenic back pain can be initiated by tissue disruption, and amplified by inflammation and infection. Healing is possible in the outer annulus only, where cell density is highest. We conclude that some discs degenerate because they are disrupted by excessive mechanical loading. This can occur without trauma if tissues are weakened by age and genetic inheritance. Moderate mechanical loading, in contrast, strengthens all spinal tissues, including discs.

Significance of cartilage endplate within herniated disc tissue.

PURPOSE: Disc herniations sometimes contain hyaline cartilage fragments, but their origins and significance are uncertain. METHODS: Herniations were removed surgically from 21 patients (aged 35-74 years) whose main symptom was sciatica (10 patients) or back pain (11 patients). Frozen sections, 5 µm thick, were examined histologically, and antibodies were used to label the matrix-degrading enzyme MMP 1, pro-inflammatory mediator TNFα, and cell proliferation marker Ki-67. Proportions of each tissue type were quantified by image analysis. Cartilage and bone components of the endplate were examined in 7-µm frozen sections from 16 cadaveric spines, aged 61-98 years. RESULTS: Cartilage fragments were found in 10/21 herniations. They averaged 5.0 mm in length, comprised 25 % of the herniation area, and two had some bone attached. Hyaline cartilage was more common in herniations from patients with sciatica (7/10) than with back pain (3/11, P = 0.050), and the area (%) of the herniation occupied by the cartilage was greater in sciatica patients (P < 0.05). Cartilage fragments showed little evidence of swelling, proteoglycan loss or inflammatory cell invasion, although cell clustering was common, and TNFα was sometimes expressed. Each cartilage fragment showed at least one straight edge, as if it had been peeled off the bony endplate, and this mechanism of failure was demonstrated in preliminary mechanical experiments. CONCLUSION: Disc herniations often include hyaline cartilage pulled from the vertebral endplates. Cartilage fragments show little swelling or proteoglycan loss, and may be slow to resorb, increasing the risk of persisting sciatica. Loss of cartilage will increase endplate permeability, facilitating endplate inflammation and disc infection.

Intervertebral disc degeneration: evidence for two distinct phenotypes.

We review the evidence that there are two types of disc degeneration. 'Endplate-driven' disc degeneration involves endplate defects and inwards collapse of the annulus, has a high heritability, mostly affects discs in the upper lumbar and thoracic spine, often starts to develop before age 30 years, usually leads to moderate back pain, and is associated with compressive injuries such as a fall on the buttocks. 'Annulus-driven' disc degeneration involves a radial fissure and/or a disc prolapse, has a low heritability, mostly affects discs in the lower lumbar spine, develops progressively after age 30 years, usually leads to severe back pain and sciatica, and is associated with repetitive bending and lifting. The structural defects which initiate the two processes both act to decompress the disc nucleus, making it less likely that the other defect could occur subsequently, and in this sense the two disc degeneration phenotypes can be viewed as distinct.

Vertebral deformity arising from an accelerated "creep" mechanism.

INTRODUCTION: Vertebral deformities often occur in patients who recall no trauma, and display no evident fracture on radiographs. We hypothesise that vertebral deformity can occur by a gradual creep mechanism which is accelerated following minor damage. "Creep" is continuous deformation under constant load. MATERIALS AND METHODS: Forty-five thoracolumbar spine motion segments were tested from cadavers aged 42-92 years. Vertebral body areal BMD was measured using DXA. Specimens were compressed at 1 kN for 30 min, while creep in each vertebral body was measured using an optical MacReflex system. After 30 min recovery, each specimen was subjected to a controlled overload event which caused minor damage to one of its vertebrae. The creep test was then repeated. RESULTS: Vertebral body creep was measurable in specimens with BMD <0.5 g/cm(2). Creep was greater anteriorly than posteriorly (p < 0.001), so that vertebrae gradually developed a wedge deformity. Compressive overload reduced specimen height by 2.24 mm (STD 0.77 mm), and increased vertebral body creep by 800 % (anteriorly), 1,000 % (centrally) and 600 % (posteriorly). In 34 vertebrae with complete before-and-after data, anterior wedging occurring during the 1st creep test averaged 0.07° (STD 0.17°), and in the 2nd test (after minor damage) it averaged 0.79° (STD 1.03°). The increase was highly significant (P < 0.001). Vertebral body wedging during the 2nd creep test was proportional to the severity of damage, as quantified by specimen height loss during the overload event (r (2) = 0.51, p < 0.001, n = 34). CONCLUSIONS: Minor damage to an old vertebral body, even if it is barely discernible on radiographs, can accelerate creep to such an extent that it makes a substantial contribution to vertebral deformity.

Biomechanics of vertebral compression fractures and clinical application.

Local biomechanical factors in the etiology of vertebral compression fractures are reviewed. The vertebral body is particularly vulnerable to compression fracture when its bone mineral density (BMD) falls with age. However, the risk of fracture, and the type of fracture produced, does not depend simply on BMD. Equally important is the state of degeneration of the adjacent intervertebral discs, which largely determines how compressive forces are distributed over the vertebral body. Disc height also influences load-sharing between the vertebral body and neural arch, and hence by Wolff's Law can influence regional variations in trabecular density within the vertebral body. Vertebral deformity is not entirely attributable to trauma: it can result from the gradual accumulation of fatigue damage, and can progress by a quasi-continuous process of "creep". Cement injection techniques such as vertebroplasty and kyphoplasty are valuable in the treatment of these fractures. Both techniques can stiffen a fractured vertebral body, and kyphoplasty may contribute towards restoring its height. The presence of cement can limit endplate deformation, and thereby partially reverse the adverse changes in load-sharing which follow vertebral fracture. Cement also reduces time-dependent "creep" deformation of damaged vertebrae.

A predictive model for creep deformation following vertebral compression fractures.

Many vertebral compression fractures continue to collapse over time, resulting in spinal deformity and chronic back pain. Currently, there is no adequate screening strategy to identify patients at risk of progressive vertebral collapse. This study developed a mathematical model to describe the quantitative relationship between initial bone damage and progressive ("creep") deformation in human vertebrae. The model uses creep rate before damage, and the degree of vertebral bone damage, to predict creep rate of a fractured vertebra following bone damage. Mechanical testing data were obtained from 27 vertebral trabeculae samples, and 38 motion segments, from 26 human spines. These were analysed to evaluate bone damage intensity, and creep rates before and after damage, in order to estimate the model parameter, p, which represents how bone damage affects the change of creep rate after damage. Results of the model showed that p was 1.38 (R2 = 0.72, p < 0.001) for vertebral trabeculae, and 1.48 for motion segments (R2 = 0.22, p = 0.003). These values were not significantly different from each other (P > 0.05). Further analyses revealed that p was not significantly influenced by cortical bone damage, endplate damage, disc degeneration, vertebral size, or vertebral areal bone mineral density (aBMD) (P > 0.05). The key determinant of creep deformation following vertebral compression fracture was the degree of trabecular bone damage. The proposed model could be used to identify the measures of bone damage on routine MR images that are associated with creep deformation so that a screening tool can be developed to predict progressive vertebral collapse following compression fracture.

Associations Between Intervertebral Disc Degeneration Grading Schemes and Measures of Disc Function.

Disc degeneration is a major cause of spinal dysfunction and pain, but grading schemes concentrate on tissue changes rather than altered function. The aim of this study was to compare disc degeneration grading systems with each other, and with biomechanical measures of disc function. Sixty-six motion segments (T8-9 to L5-S1) were dissected from cadavers aged 48-98 years. Disc function was assessed by measuring nucleus pressure (IDP) and maximum stresses in the annulus under 1 kN of compression. Detailed "scores" of disc degeneration were based on independent radiographic, macroscopic, and microscopic evaluations. For each evaluation, scores were used to assign a degeneration "grade" (I-IV), and functional measures were then correlated with degeneration scores and grades. Results showed that all measures were reliable (intraclass correlation coefficients: 0.82-0.99). Macroscopic and microscopic assessments were highly correlated with each other (r: 0.57-0.89, p < 0.001) but only weakly correlated with radiographic features. The overall macroscopic and microscopic scores of degeneration increased significantly with age and at lower spinal levels, although the influence of age was less marked in the case of the microscopic scores. IDP decreased with age and at lower spinal levels, but annulus stresses were more variable. Importantly, IDP and annulus stresses decreased consistently with all measures of disc degeneration, and these associations remained strong after controlling for age, gender, and spinal level. We conclude that radiographic and tissue-based assessments of disc degeneration are consistent with each other, and are more closely related to mechanical (dys)function than to age or spinal level. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1946-1955, 2019.